Sepsis-Induced Coagulopathy Score is Associated with an Increased Risk of New-Onset Atrial Fibrillation in Septic Patients: A Two-Centered Retrospective Study.

Purpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis. Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate. Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses. Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.

Altered immune pathways in patients of temporal lobe epilepsy with and without hippocampal sclerosis.

Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein-protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Effect of early antibiotic treatment strategy on prognosis of acute pancreatitis.

BACKGROUND: Antibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP). MATERIALS AND METHODS: Clinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset. RESULTS: A total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP. CONCLUSION: Strategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.

Polymyxin B-induced skin hyperpigmentation: a rare case report and literature review.

BACKGROUND: Polymyxin B (PMB), which is regarded as the ultimate antibacterial treatment against some intractable gram-negative bacteria with its outstanding anti-bacterial activities, inflicts several adverse effects on patients. However, skin hyperpigmentaion (SH) induced by PMB is very rare. Here, we report a case of polymyxin B-induced skin hyperpigmentation (PMB-iSH) in a 21-year-old female. To the best of our knowledge, this is the first case of PMB-iSH in China. CASE PRESENTATION: A 21-year-old female patient with sepsis received the administration of PMB by intravenous injection for the treatment of multi-drug resistant Klebsiella pneumoniae (MDR-KP) infection. She later suffered from a rare adverse drug reaction (ADR), namely PMB-iSH, after 5-day PMB administration during her treatment. There were multiple red rashes spread on the whole body skin at first. With the rashes fading away, SH with dark round spots appeared, associated with no pain or pruritus. The skin of the head and neck was darkened evidently, and dark brown spots were spread on the skin of trunk and limbs. About a month after her admission, urged by the relatives, the patient was transferred back to the local hospital for further treatment in the end, and her skin color didn't recover to the previous state at that time. CONCLUSION: Both our case and the literature review highlight that PMB can give rise to SH indeed. Clinicians and pharmacists should attach great importance to this rare pigmentary disorder and further investigation is warranted.

[Research of optimal dosing regimens and therapeutic drug monitoring for vancomycin by clinical pharmacists: analysis of 7-year data].

OBJECTIVE: To investigate the effectiveness and safety of clinical pharmacists-directed vancomycin dosing and therapeutic drug monitoring (TDM), and to promote the individualized medication of vancomycin. METHODS: Information of hospitalized patients treated by vancomycin admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to October 2017 was collected retrospectively during study period, the patients were divided into pharmacists intervention and non-pharmacists intervention groups according to pharmacist-directed vancomycin dosing guideline or not. The individualized dosing regimen of vancomycin for the patients in pharmacists intervention group was guided by clinical pharmacists, this guideline was that pharmacists offered the TDM guidance, made the individualized dosage regimen of vancomycin, etc., which based on the patients' pathophysiology, condition, and the adjustments of increased dose or 24-hour continuous infusion vancomycin were made for patients if the steady-state trough concentrations fell below the target level. Vancomycin dosage was made for patients in the non-pharmacists intervention group by physicians only based on vancomycin instructions or clinical experience. The vancomycin dosing, TDM, microorganism culture, renal function, 30-day mortality rate, and length of hospital stay were recorded. The appropriateness of TDM for vancomycin was defined as a blood collection within 1 hour of the next scheduled dose after steady state achieved. The rationality of the initial dosing regimen was determined based on the vancomycin application guidelines issued by Infectious Diseases Society of America (IDSA) in 2009. RESULTS: A total of 258 patients were enrolled, and there were 158 patients in the non-pharmacists intervention group and 100 in pharmacists intervention group. The appropriateness of TDM for vancomycin in pharmacists intervention group was significantly improved as compared with that in non-pharmacists intervention group [87.0% (87/100) vs. 69.6% (110/158), P < 0.01], the percentage of first trough serum concentrations drawn on day 3 after steady state achieved was significantly increased [51.0% (51/100) vs. 37.3% (53/142), P < 0.05]. Compared with the non-pharmacists intervention group, the percentages of patients who received appropriate initial dosing and attained the initial target therapeutic range in pharmacists intervention group were significantly increased [87.4% (76/87) vs. 68.2% (75/110), 51.7% (45/87) vs. 30.9% (34/110), both P < 0.01], the percentage of patients whose vancomycin dosing regimen was adjusted based on TDM results was also significantly increased [54.0% (47/87) vs. 15.5% (17/110), P < 0.01], the rate of vancomycin serum concentrations reaching the standard was increased [70.1% (61/87) vs. 32.7% (36/110), P < 0.01], and a lower number of patients in sub- or supra-therapeutic range was observed in pharmacists intervention group [27.6% (24/87) vs. 46.4% (51/110), 2.3% (2/87) vs. 20.9% (23/110), both P < 0.01]. In addition, a lower incidence of vancomycin-induced acute kidney injury (AKI) was observed in pharmacists intervention group as compared with that in non-pharmacists intervention group [0 (0/87) vs. 6.4% (7/110), P < 0.01]. No significant difference was observed in the microorganism culture, 30-day mortality rate or length of hospital stay between the two groups. Among the 87 patients in pharmacists intervention group, the vancomycin dosing was adjusted for 42 patients who did not attain the target therapeutic range, increasing the dose of vancomycin was made for 22 patients, 24-hour continuous infusion was made for 20 patients. Compared with the only increasing vancomycin dose group, vancomycin continuous infusion for 24 hours could significantly increase the serum trough concentration (mg/L: 18.0±6.7 vs. 12.5±5.8, P < 0.05), and reduce daily dosage (mg/kg: 27.1±7.1 vs. 36.6±9.2, P < 0.01). CONCLUSIONS: The implementation of a pharmacist-directed vancomycin dosing guideline based on TDM optimized vancomycin dosing regimen, improved the accuracy and timeliness of TDM for vancomycin, achieved a higher percentage of levels within the therapeutic range, and a lower incidence of vancomycin-induced AKI.

Diagnostic outcomes of magnetocardiography in patients with coronary artery disease.

OBJECTIVE: To evaluate the diagnostic outcomes of magnetocardiography (MCG) on the patients with coronary artery disease and compared the outcomes between MCG, ECG and Echocardiography. METHODS: MCG measurements were performed on 101 patients with coronary artery disease and 116 healthy volunteers with a seven-channel magnetocardiographic system (MCG7, SQUID AG, Germany) installed in an unshielded room. CAD was diagnosed when stenosis ≥ 70% in ≥ 1 vessel. Three quantitative indicators were analyzed, R-max/T-max ratio, R value and á average angle. RESULTS: R-max/T-max ratio of CAD group (6.30 ± 4.07) was much higher than that of healthy group (3.73 ± 1.41) (P < 0.001), R value of CAD group (69.16 ± 27.87)% was significantly higher than that of healthy group (34.96 ± 19.09)% (P < 0.001), á average angle of CAD group (221.46° ± 64.53°) was higher than that of healthy group (24.32° ± 20.70°) (P < 0.01). In 75 of 101 CAD patients (74.26%), MCG had abnormal mapping patterns. The resting ECG examination showed ischemic changes, such as abnormal Q waves and ST-T change in 49 patients (48.51%). Echocardiography revealed abnormal left ventricular wall motion and asynergy in 46 patients (45.54%). Thus, the diagnostic outcomes of MCG for the patients with CAD were much significant than those of ECG and echocardiography (P < 0.001). CONCLUSIONS: Our result showed that resting MCG under condition of an advanced data analysis has higher diagnostic outcomes and is superior to ECG or echocardiography for patients with CAD. MCG can detect ST-segment displacement caused by ischemic myocardium, thus helpful in diagnosing coronary artery disease early.

Changes in the composition of the thoracic aortic wall in spontaneously hypertensive rats treated with losartan or spironolactone.

1. In the present study, we compared the elastin and collagen content of thoracic aortic medial and adventitial layers from Wistar-kyoto (WKY) and spontaneously hypertensive rats (SHR). In addition, the effects of losartan, an angiotensin II receptor antagonist, and spironolactone, a mineralocorticoid receptor antagonist, on collagen and elastin content were determined. 2. Prehypertensive (4-week-old) and hypertensive (16-week-old) SHR were randomly divided into three groups treated with either 0.9% NaCl, losartan (20 mg/kg per day) or spironolactone (200 mg/kg per day). Prehypertensive and hypertensive SHR were treated for 12 and 16 weeks, respectively. Age-matched WKY rats were not treated with NaCl, losartan or spironolactone and served as the control group. 3. The medial and adventitial layers of the thoracic aorta were composed mainly of elastin and collagen, respectively, in both SHR and WKY rats. Compared with WKY rats, SHR exhibited greater collagen and elastin content in the media, but decreased collagen and elastin content in the adventitial layer. Both medial and adventitial collagen and elastin content increased significantly with age in both strains and was greater in 32-week-old rats compared with 16-week-old rats. Spironolactone treatment decreased collagen content in the media of thoracic aortas from prehypertensive SHR, whereas losartan decreased collagen content in the media of aortas from hypertensive SHR. In contrast, neither spironolactone nor losartan had any effect on adventitial collagen content in prehypertensive and hypertensive SHR. Medial collagen and elastin were positively related to pulse pressure (PP), but there was no correlation between adventitial mass or collagen content and PP or mean arterial pressure in untreated and treated SHR and WKY rats. 4. In conclusion, the composition of the medial and adventitial layers of the thoracic aorta differs and treatment of SHR with losartan and spironolactone decreases collagen content when delivered at the hypertensive or prehypertensive stage, respectively. However, neither drug has any effect on adventitial collagen content in SHR.

Angiotensin II-stimulated collagen synthesis in aortic adventitial fibroblasts is mediated by connective tissue growth factor.

Angiotensin II (Ang II), a potent mediator of vascular remodeling, can stimulate the synthesis of extracellular matrix in vascular cells. Recent studies indicate that connective tissue growth factor (CTGF) is involved in collagen synthesis. There is also increasing evidence that adventitial fibroblasts (AFs) are actively involved in vascular remodeling. However, whether collagen synthesis by AFs is mediated by CTGF, or whether it is relevant to Ang II, has not been studied. The present study was conducted to determine whether CTGF is expressed in AFs, and if so, whether the CTGF produced by AFs participates in collagen synthesis. The AFs were isolated from thoracic aorta of Wistar-Kyoto rats (WKY). The expression of CTGF was measured by Western blot or real-time PCR. Collagen synthesis was assessed by [(3)H]proline incorporation. Our results suggested that CTGF was expressed in AFs and secreted into medium. Ang II increased CTGF mRNA and protein expression in a time- and dose-dependent manner, with the maximal protein increase occurring at 24 h with an Ang II dose of 10(-7) mol/L, and this increase was inhibited by the Ang II receptor type 1 (AT(1)-R) antagonist losartan, but not by the Ang II receptor type 2 (AT(2)-R) antagonist PD123319. Ang II dose-dependently stimulated the incorporation of [(3)H]proline into cultured AFs, and this effect was inhibited by a CTGF antisense oligodeoxynucleotide. Overexpression of CTGF by pcDNA3.1(+)/CTGF increased [(3)H]proline incorporation in cultured AFs. The results demonstrated that, in cultured AFs, Ang II increased CTGF production via AT(1)-R, which could be mediators of collagen synthesis by Ang II. This finding suggests that CTGF might be a novel target for antifibrotic therapy in vascular diseases.

NAD(P)H oxidase-derived reactive oxygen species regulate angiotensin-II induced adventitial fibroblast phenotypic differentiation.

Phenotypic differentiation of adventitial fibroblasts into myofibroblasts is an essential feature of vascular remodeling. The present study was undertaken to test the hypothesis that reactive oxygen species (ROS) are involved in rat adventitial fibroblast differentiation to myofibroblast. Activation of alpha-smooth muscle actin (alpha-SMA) was used as a marker of myofibroblast. Angiotensin II increased intracellular ROS in adventitial fibroblasts that was completely inhibited by the free radical scavenger NAC, the NAD(P)H oxidase inhibitor DPI, and transfection of antisense gp91phox oligonucleotides. Myofibroblast differentiation was prevented by inhibition of ROS generation with DPI, NAC, and antisense gp91phox as shown by decreased expression of alpha-SMA. Angiotensin II rapidly induced phosphorylation of p38 MAPK and JNK, both of which were inhibited by DPI, NAC, antisense gp91phox, and the selective AT1 receptor antagonist, losartan. Inhibiting p38MAPK with SB202190 or JNK with SP600125 also reduced angiotensin II-induced alpha-SMA expression. These findings demonstrate that angiotensin II induces adventitial fibroblast differentiation to myofibroblast via a pathway that involves NADPH oxidase generation of ROS and activation of p38MAPK and JNK pathways.

Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs.

AIM: To investigate the hypothesis that transplantation with expanded autologous endothelial progenitor cells (EPC) could enhance neovascularization. METHODS: Peripheral blood mononuclear cells (PB-MNC) isolated from New Zealand White rabbits were cultured in vitro. At d 7, the adherent cells were collected for autologous transplantation. Rabbits with severe unilateral hind limb ischemia were randomly assigned to receive phosphate-buffered saline or expanded EPC in phosphate-buffered saline, administered by intramuscular injection in 6 sites of the ischemic thigh at postoperative d 7. Neovascularization was monitored by using the calf blood pressure ratio to indicate tissue perfusion, digital subtraction angiography to identify collateral vessel development and histological analysis of capillary density in the ischemic limb at d 35 after surgery. RESULTS: Autologous EPC transplantation produced significant amelioration in ischemic hind limbs, as indicated by a greater calf blood pressure ratio (0.52+/-0.04 vs 0.42+/-0.05, P<0.01), angiographic score (1.44+/-0.06 vs 0.98+/-0.08, P<0.01) and capillary density in muscle (195.2+/-5.4/mm2 vs 169.4+/-6.4/mm2, P<0.05), than controls. CONCLUSION: Transplantation of autologous expanded EPC can promote neovascularization in ischemic hindlimbs.